Deranged expression of follistatin and follistatin-like protein in women with ovarian endometriosis

ObjectiveTo evaluate the messenger RNA (mRNA) expression and peptide localization of follistatin and follistatin-like protein (FLRG) in ovarian endometriosis, compared to healthy human endometrium.DesignSamples of ovarian endometriotic and healthy endometrial tissues were processed by semiquantitative reverse transcript ase-polymerase chain reaction and immunohistochemistry.SettingAcademic health centers in Siena, Italy, and Belo Horizonte, Brazil.Patient(s)Women with endometrioma who underwent laparoscopic excision of ovarian endometriotic cysts (n = 16), and healthy, nonpregnant women (n = 18, control group).Main Outcome Measure(s)Immunostaining and relative quantification of follistatin and FLRG mRNA in ovarian endometriosis and eutopic endometrium.Result(s)Both ovarian endometriosis and healthy endometrium expressed and localized follistatin and FLRG. In endometriotic glands, follistatin immunostaining was homogeneously distributed throughout the cytoplasm of the epithelial cells, contrasting with normal eutopic endometrium, where follistatin expression was focal, irregular, and confined to the basal side of the glands. Follistatin-like protein was immunolocalized in the nuclei of both glandular epithelial cells and stromal cells, with less intense staining in endometriotic samples. The relative intensity of follistatin and FLRG immunostaining was significantly higher and lower, respectively, in endometriosis than in controls. The expression of follistatin mRNA was higher, while that of FLRG mRNA was lower, in ovarian endometriosis than in healthy eutopic endometrium.Conclusion(s)Ovarian endometriotic lesions show a deranged expression of FLRG and follistatin, which are activin A-binding proteins. This may result in an altered effect of activin A on angiogenesis and/or endometrial differentiation.